Analysis of carbamazepine side effects associated with bone metabolism, folate and vitamin B12 serum levels in Isfahan epileptic patients
Abstract
According to previous publications, chronic uses of AEDs reduce bone health, increase homocysteine levels, alkaline phosphates and many other biochemical changes. The aim of this study was to investigate carbamazepine (CBZ) effects on bone density, serum levels of folate, vitamin B12 and other biochemical variables. Twenty-one adult epileptic patients who received CBZ for treatment of epileptic attacks were enrolled. Bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry method. Biochemical indices of bone metabolism, including serum calcium, phosphorus, alkaline phosphatase contents and also serum levels of folate, vitamin B12, homocysteine were measured. All clinical, laboratory and pharmacological data were recorded in d-Base and analyzed using SPSS (version 16) for windows. BMD Z-scores, and 25-dihydroxyvitamin D3 concentrations was not differ significantly, but it seems that, the female patients had diminished BMD at the femoral neck (p≤ 0.05). Folate or vitamin B12 levels tend toward lower values. This seems to be connected to a tendency toward higher mean corpuscular volume (MCV) with a mean of 84.9 fl (ranged from 59-120 fl). TWithin the population studied, there was no correlation between CBZC0 and homocysteine levels (p≤ 0.63). In compare to normal value the serum calcium content was lower with a mean of 7.8 mg/dl (ranged; 7.0-8.9 mg/dl; p ≤ 0.04). With a mean of 213 U/L serums alkaline phosphatase was significantly higher (p ≤ 0.01) than normal values. Due to the need for chronic prescription strategy in order to control convulsion attack, pharmacotherapy with AEDs may consequence to changes in serum contents of calcium, phosphorus, alkaline phosphatase in addition to decrease in BMD and increase in homocysteine levels. Further studies related to efficacy and side-effects of CBZ as the most prescribed AEDs in Iranian epileptic population seem to be valuable.
Keywords
Full Text:
PDFReferences
Meier C, Marius E. Kraenzlin. Antiepileptics and Bone Health. Ther Adv Musculoskelet Dis. 2011 October; 3(5): 235–243. PMID: 22870482 [PubMed] PMCID: PMC3383529
Tolou Ghamari Z. Antiepileptic Drugs (AEDs) Polypharmacy could lead to buried pharmacokinetic interactions due to CYP450. Drug Metab Lett 2012.PMID: 23140557 [PubMed - indexed for MEDLINE]
Tolou Ghamari Z, Najafi MR, Mehvari-Habibabadi J, Zare M. Preliminarily analysis of carbamazepine (CBZ) C0 in patients visited Isfahan epileptic clinics. Int J Prev Med. 2013; Suppl 2 S343–S346. PMID: 23776749 [PubMed] PMCID: PMC3678243
Tolou Ghamari Z, Zare M, Mehvari-Habibabadi J, Najafi MR. Antiepileptic Drugs: A consideration of clinical and biochemical outcome in patients with epilepsy. Int J Prev Med. 2013; Suppl 2 S330–S337. PMID: 23776747 [PubMed] PMCID: PMC3678241
Tolou-Ghamari Z, Zare M, Mehvari-Habibabadi J, Najafi MR. A quick outlook to the world of carbamazepine pharmacokinetics in epilepsy from 1953 to 2012. Supplement 1 March 2013. JRMS. PMID: 23961295 [PubMed] PMCID: PMC3743329
Kumar V, Aggarwal A, Sharma S, Chillar N, Mittal H, Faridi MM. Effect of carbamazepine therapy on homocysteine, vitamin B12 and folic acid levels in children with epilepsy. Indian Pediatr. 2013 May 8;50(5):469-72. PMID: 23255689 [PubMed - indexed for MEDLINE]
Lee RH, Lyles KW, Sloane R, Colón-Emeric C. The association of newer anticonvulsant medications and bone mineral density. Endocr Pract. 2012 Sep 14:1-22. PMID: 22982796 [PubMed - as supplied by publisher] PMCID: PMC3769485
Turan MI, Cayir A, Ozden O, Tan H. An Examination of the Mutual Effects of Valproic Acid, Carbamazepine, and Phenobarbital on 25-Hydroxyvitamin D Levels and Thyroid Function Tests. Neuropediatrics. 2013 Jul 25. PMID: 23888467 [PubMed - indexed for MEDLINE]
Wang Z, Lin YS, Dickmann LJ, Poulton EJ, Eaton DL, Lampe JW, Shen DD, Davis CL, Shuhart MC, Thummel KE. Enhancement of hepatic 4-hydroxylation of 25-hydroxyvitamin D3 through CYP3A4 induction in vitro and in vivo: implications for drug-induced osteomalacia. J Bone Miner Res. 2013 May;28(5):1101-16. PMID: 23212742 [PubMed - indexed for MEDLINE] PMCID: PMC3609874
French JA, Faught E. Rational polytherapy. Epilepsia 2009; 50 Suppl 8: 63-8. PMID: 19702736 [PubMed - indexed for MEDLINE]
Kir HM, Garip S, Sahin D, Öztaş B. Effects of carbamazepine on serum parathormone, 25- hydroxyvitamin D, bone specific alkaline phosphatase, C-telopeptide, and osteocalcin levels in healthy rats. Bosn J Basic Med Sci. 2012 Nov;12(4):240-4.PMID: 23198939 [PubMed - indexed for MEDLINE] PMCID: PMC4362499
Brodie MJ, Mintzer S, Pack AM, Gidal BE, Vecht CJ, Schmidt D. Enzyme induction with antiepileptic drugs: cause for concern? Epilepsia. 2013 Jan;54(1):11-27. PMID: 23016553 [PubMed - indexed for MEDLINE]
Aksoy A, Sönmez FM, Deger O, Hosver I, Karagüzel G. The effects of antiepileptic drugs on the relationships between leptin levels and bone turnover in prepubertal children with epilepsy. J Pediatr Endocrinol Metab. 2011;24(9-10):703-8. PMID: 22145460 [PubMed - indexed for MEDLINE]
Heo K, Rhee Y, Lee HW, Lee SA, Shin DJ, Kim WJ, Song HK, Song K, Lee BI. The effect of topiramate monotherapy on bone mineral density and markers of bone and mineral metabolism in premenopausal women with epilepsy. Epilepsia. 2011 Oct;52(10):1884-9. PMID: 21692779 [PubMed - indexed for MEDLINE]
Pack AM. Treatment of epilepsy to optimize bone health. Curr Treat Options Neurol. 2011 Aug;13(4):346-54. PMID: 21557040 [PubMed]
Lambrinoudaki I, Kaparos G, Armeni E, Alexandrou A, Damaskos C, Logothetis E, Creatsa M, Antoniou A, Kouskouni E, Triantafyllou N. BsmI vitamin D receptor's polymorphism and bone mineral density in men and premenopausal women on long-term antiepileptic therapy. Eur J Neurol. 2011 Jan;18(1):93-8. PMID: 20500803 [PubMed - indexed for MEDLINE
Lee RH, Lyles KW, Colon-Emeric C. A Review of the Effect of Anticonvulsant Medications on Bone Mineral Density and Fracture Risk. Am J Geriatr Pharmacother. 2010 February; 8(1): 34–46. PMID: 20226391 [PubMed - indexed for MEDLINE] PMCID: PMC3570810
Karabiber H, Sonmezgoz E, Ozerol E, Yakinci C, Otlu B, Yologlu S. Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid. Brain Dev. 2003;25(2):113–5. PMID: 12581807 [PubMed - indexed for MEDLINE]
Kurul S, Unalp A, Yis U. Homocysteine levels in epileptic children receiving antiepileptic drugs. J Child Neurol. 2007;22(12):1389–92. doi: 10.1177/0883073807307081.
Zeitlhofer J, Doppelbauer A, Tribl G, Leitha T, Deecke L. Changes of serum lipid patterns during long-term anticonvulsive treatment. Clin Investig. 1993;71(7):574–8. PMID: 8374254 [PubMed - indexed for MEDLINE]
Dorszewska J, Winczewska-Wiktor A, Sniezawska A, Kaczmarek I, Steinborn B. Homocysteine and asymmetric dimethylarginine (ADMA) in epilepsy. Przegl Lek. 2009; 66(8):448-52. PMID: 20043592 [PubMed - indexed for MEDLINE]
Linnebank M, Moskau S, Semmler A, Widman G, Stoffel-Wagner B, Weller M, Elger CE. Antiepileptic drugs interact with folate and vitamin B12 serum levels. Ann Neurol. 2011 Feb;69(2):352-9. doi: 10.1002/ana.22229. Epub 2011 Jan 19.
Misra A, Aggarwal A, Singh O, Sharma S. Effect of carbamazepine therapy on vitamin D and parathormone in epileptic children. Pediatr Neurol. 2010 Nov;43(5):320-4. PMID: 20933174 [PubMed - indexed for MEDLINE]
Nakken KO, Taubøll E. Bone loss associated with use of antiepileptic drugs. Expert Opin Drug Saf. 2010 Jul;9(4):561-71. PMID: 20201711 [PubMed - indexed for MEDLINE]
Najafi MR, Chitsaz A, Saberi K, Saberi A. The comparison of plasma homocystein in Parkinson disease: mild with sever disease. Medical Journal of Mashahad University of medical Sciences, Vol. 49, No 94, P: 401-406, Winter 2007.
Refbacks
- There are currently no refbacks.